One of the puzzles about Zika virus and its newly discovered penchant to cause fetal anomalies is understanding why these facts about Zika are being noticed now given relatively large outbreaks of the virus that occurred in Micronesia and French Polynesia. In those outbreaks, complications such as Guillain-Barre Syndrome were noted but not microcephaly was noted (French Polynesia recently reported 8 microcephaly cases from their outbreak).

One tantalizing hypothesis which is gaining evidence is the role of preexisting dengue antibodies. Dengue, a flavivirus like Zika, has the ability to cause severe disease by employing preexisting antibodies to one strain to enhance infection with another. This phenomenon is known as antibody-dependent enhancement and was discovered by Dr. Scott Halstead who, early on, thought this was playing a role with Zika.

Now, evidence is beginning to be presented that shows that this may be more than a hypothesis. A pre-publication paper published by researchers at Florida Gulf Coast University illustrates that dengue monoclonal antibodies and immune sera both have the potential to enhance Zika infection in a cell culture model.

These preliminary findings were pathbreaking in their own right but yesterday at the Cura Zika symposium at the University of Pittsburgh's School of Public Health a leading Zika researcher at the institute presenting some extremely important data on this phenomenon that deserve a wide audience.

Dr. Ernesto Marquez, working out of Recife, presented data illustrating that in Brazil -- as opposed to Southeast Asia and other other areas in which dengue and Zika co-circulate --monotypic infection is much more common. What this means is that Recife women are more likely to have been infected with just 1 (out of 4 strains) of dengue than in Thailand where multi-typic infection is the norm. DENV-3 is the

What Marquez noted in his data was the almost unique association of DENV-3 to enhance infection. There is much more to this presentation and much nuance to how these antibodies work (for example, their quantity) so I suggest watching it online. It is a great example of how scientific analysis proceeds.

The obvious policy question that comes to mind is how would the dengue vaccine, approved for use in Brazil, Mexico, and the Philippines, interact with Zika? Would it foster antibody dependent enhancement? Or would it be protective? Other questions to answer would involve looking at case-control data between dengue-naive and non-naive pregnant women who are infected and assessing how their clinical courses may differ.

Nonetheless, science is advancing quite rapidly on this fascinating virus.